tbuckley/cabot-search huggingface dataset:
Impact of endocrine therapy adherence on racial disparities in breast cancer survival.
Authors: Kimberley T Lee, Melanie Buhlmann, Clement K Gwede, L. Robert Gore, I-Wen Pan, Yi Luo, Shelley S Tworoger, Susan Thomas Vadaparampil, Heather S.L. Jim
Journal: Journal of Clinical Oncology (2023)

541 Background: Black women have worse breast cancer outcomes compared to their White counterparts, even for hormone receptor positive (HR+) HER2 negative (HER2-) breast cancer (BC). This tumor type is usually treated with 5-10 years of adjuvant endocrine therapy (ET) to reduce risk of BC recurrence and improve survival. We investigated the impact of adherence to ET on racial differences in survival for HR+ HER2- BC survivors. Methods: We conducted a population-based, retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, which links demographic and clinical data with cause of death for persons with cancer and Medicare claims for covered health services. We examined 9,039 women with HR+ HER2- stage I-III BC diagnosed between 2007 and 2016, who received primary breast surgery and initiated ET. Adherence to ET was measured using the medication possession ratio (MPR), which assesses the proportion of time a patient has medication available via filled prescriptions. As in established literature, we defined ET adherence as MPR &gt; = 80%. Causal mediation analysis was performed to measure to impact of adherence on survival disparities between Black and White BC survivors. Results: Mean age at diagnosis was 72 years, 6.5% were Black, and 20.9% were dual eligible for Medicaid (a surrogate for socioeconomic hardship). Most had stage I or II breast cancer (69.3%) and mastectomy as primary surgery (69.7%). Nineteen percent received chemotherapy and 62.5% received radiation. In univariate analyses, factors associated with ET adherence were Black race (OR 0.62, 95% CI 0.54-0.75), insured by Medicaid (OR 0.72, 95% CI 0.65-0.81), being married (OR 1.14, 95% CI 1.03-1.25), and increased comorbidities (Charlson score &gt; = 2) (OR 0.88, 95% CI 0.78-0.99). Age, BC stage, type of surgery, and receipt of chemotherapy or radiation were not associated with ET adherence. In multivariable models adjusting for age, race, marital status, Medicaid eligibility, and Charlson score, Black race and Medicaid eligibility remained inversely associated with ET adherence (OR 0.70, 95% CI 0.59-0.83 and OR 0.77, 95% CI 0.69-0.87 respectively). Among those who were adherent to ET, Black women had 43% higher risk of mortality compared to White women (HR 1.43, 95% CI 1.17-1.76). In mediation analysis, 4.25% of the observed survival disparity between Black and White women can be explained by differences in ET adherence. Conclusions: We identified racial disparities in ET adherence and overall survival among women with BC. Adherence to ET accounted for a small percentage of racial disparities in survival. Further research is needed to delineate other factors contributing to ET non-adherence among Black women and to investigate additional factors contributing to known disparities in BC survival.
Effect of microRNA-21 blockade in human triple negative breast cancer allografts on progression and immune checkpoint proteins.
Authors: Yuan-Yuan Jin, Vilas Shivaji Desai, Miguel M. Castro, Edith P. Mitchell, Eric Wickstrom
Journal: Journal of Clinical Oncology (2023)

e13097 Background: Triple negative breast cancer (TNBC) is an orphan disease that attacks &gt; 46,000 US women every year. TNBC recurs after standard-of-care surgery, chemotherapy and radiation, killing half its victims within 4 years. Poly(ADP-ribose) polymerase (PARP) inhibitors, topoisomerase inhibitors, immune checkpoint inhibitors, and antibody-drug conjugates extend the survival of a fraction of TNBC patients for a few months. Thus, TNBC shows a critical need for molecularly-targeted therapy. Most TNBC cells show high microRNA 21 (miR-21), identical in humans and mice, which decreases tumor suppressor proteins that keep cell growth in check. Hypothesis: Short anti-miR-21 RNA analogs conjugated to a receptor ligand will direct TNBC cell uptake and slow the growth of TNBC orthotopic allografts with immune activation and minimal toxicity. Methods: We designed an anti-miR-21 RNA analog using aminomethyl bridged nucleic acid (BNA), exhibiting low toxicity, and serum stability. We lipofected a concentration ramp of the anti-miR-21 RNA analog into human TNBC cell lines (MDA-MB-231, MDA-MB-157, MDA-MB-436, MDA-MB-468, BT-20, BT-549, HCC1806, HCC1937, HCC1806) representing a spectrum of TNBC subtypes, then measured proliferation and biochemical markers. We also conjugated a peptide analog for endocytosis by the insulin-like growth factor 1 receptor (IGF1R), overexpressed in most TNBC lesions. The peptide ligand for IGF1R provides a unique strategy for delivering the anti-miR-21 RNA analog preferentially into TNBC cells. We administered 5 mg/kg of the anti-miR-21 RNA-peptide analog in sterile saline intraperitoneally twice a week for 14 days into immunocompetent female Balb/c mice bearing syngeneic EMT6 TNBC tumors in their mammary fat pads. Results: The anti-miR-21 RNA analog slowed proliferation, increased apoptosis, elevated tumor suppressor proteins, and suppressed immune checkpoint gene expression in multiple human TNBC lines. IC50 for inhibiting cell proliferation correlated with miR-21 copies/cell in 7 TNBC cell lines, but not in the non-tumorigenic breast epithelial cell line MCF-10A. The anti-miR-21 RNA-peptide analog stopped orthotopic TNBC allograft growth in syngeneic immunocompetent female Balb/c mice during 14 days of therapy, with apparent safety. Conclusions: This strategy optimizes cancer cell-specific delivery to block proliferation and immune checkpoints. The results support further preclinical proof-of-concept studies to enable an eIND submission for the anti-miR-21 RNA-peptide analog.
Capivasertib (C) and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2– advanced breast cancer (ABC): Characterization and management of common adverse events (AEs) from the phase 3 CAPItello-291 trial.
Authors: Hope S. Rugo, Mafalda Oliveira, Sacha Jon Howell, Florence Dalenc, Javier Cortes, Henry Leonidas Gomez, Xichun Hu, Hiroji Iwata, Komal L. Jhaveri, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Yeon Hee Park, Joohyuk Sohn, Lyudmila Zhukova, Jill Logan, Ken Twomey, Mahmuda Khatun, Celina M. D'Cruz, Nicholas C. Turner
Journal: Journal of Clinical Oncology (2023)

1067 Background: In the CAPItello-291 trial in eligible pts with AI-resistant HR+/HER2– ABC, the addition of C (a potent, selective pan-AKT inhibitor) to F significantly improved PFS (primary endpoint) compared with placebo (P) in the overall (HR 0.60; 95% CI 0.51–0.71; p&lt;0.001) and AKT pathway-altered population (HR 0.50; 95% CI 0.38–0.65; p&lt;0.001). We report a detailed analysis of AEs. Methods: Pts were randomized 1:1 to receive F (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with either P or C (400 mg BID; 4 days on, 3 days off). Pts with HbA1c &lt;8.0% and diabetes not requiring insulin were eligible. Incidence, management, and time to onset were summarized for common AEs (&gt;10% any grade and &gt;2.0% grade ≥3; CTCAE v5.0). Results: Overall, 708 pts were randomized to C+F (n=355) vs P+F (n=353); safety population C+F (n=355) vs P+F (n=350). Baseline risk factors potentially associated with hyperglycemia were a history of diabetes in 34 pts (10%) in the C+F arm vs 20 pts (6%) in the P+F arm (baseline median [range] HbA1c 5.4% [4.0–8.3] vs 5.4% [3.9–7.7]), median weight 65.0 kg (34–150) vs 66.5 kg (37–147) and 54% vs 53% of pts overweight/obese in the C+F vs P+F arms, respectively. Common AEs were diarrhea, rash, and hyperglycemia; maximum AE grade was mostly 1/2 and led to low rates of discontinuation. In the C+F arm, medications for the management of AEs were used in 151/257 pts (59%) with diarrhea (mostly loperamide; n=135), 109/135 pts (81%) with rash (mostly antihistamines; n=75/topical corticosteroids; n=64), and 28/60 pts (47%) with hyperglycemia (mostly metformin; n=18). Conclusions: Diarrhea, rash, and hyperglycemia, the most commonly reported AEs associated with AKT pathway inhibition, occur early in treatment with C+F, are generally low grade and manageable, and are associated with low rates of dose modifications/discontinuations. Clinical trial information: NCT04305496 . [Table: see text]
Prognostic role of HER2 expression in patients with ER-positive/HER2-negative breast cancer: Results from a population-based cancer registry study.
Authors: Antonino Musolino, Olga Serra, Benedetta Pellegrino, Chiara Tommasi, Daniele Zanoni, Laura Cortesi, Fabio Canino, Federico Piacentini, Paolo Sgargi, Maria Michiara
Journal: Journal of Clinical Oncology (2023)

547 Background: Estrogen Receptor (ER)-positive (+)/Human Epidermal Growth Factor Receptor 2 (HER2)-negative (-) breast cancers (BCs) express variable protein levels of both ER and HER2, which can influence prognosis. Methods: We evaluated all invasive ER+/HER2- BCs (n = 3633) that were diagnosed and systematically collected by the Parma Province Cancer Registry, Italy, from 2004 to 2018. Tumors were classified by HER2 (IHC score of 0, 1+ or 2+ with negative FISH) and ER status (ER-low [1-9%], ER-moderate [10-79%] or ER-high [80-100%]). Comparisons of clinicopathologic characteristics and disease outcome were performed. Results: BCs with late-stage diagnosis ( P = 0.04), high histologic grade ( P &lt; 0.0001), or high proliferative rate ( P &lt; 0.0001) were more likely HER2 2+/FISH-. The rate of ER-high BCs did not change from 2675 of 2938 (91%) HER2 0 tumors to 508 of 560 (90.7%) HER2 1+, and 124 of 135 (91.9%) HER2 2+/FISH- tumors. Correspondingly, ER-low BCs were not enriched among HER2 0 tumors compared to the other tumors with different HER2 expression ( P = 0.6). The 5-year overall survival (OS) for HER2 2+/FISH- BCs was lower than that for HER2 0 or 1+ tumors ( P = 0.03). ER-low/moderate tumors were associated with poorer OS in comparison with ER-high BCs ( P &lt; 0.0001). HER2 2+/FISH- status was detrimental to OS among patients (pts) with ER-high tumors ( P = 0.04), while this finding was not observed among ER-low/moderate BCs ( P = 0.21). An interaction between HER2 2+/FISH- expression and ER-high status was found for poorer OS after adjusting for prognostic variables (HR = 1.7; 95% CI: 1.1-2.9). Conclusions: The prognostic role of HER2 expression in pts with ER-positive/HER2-negative BCs seems to be restricted to ER-high tumors, while the worse prognosis of tumors with lower ER expression is not associated with HER2 status. These findings may help identify optimal patient inclusion criteria for clinical trials with novel anti-HER2 therapies in ER-positive/HER2-negative disease.
Circulating methylated-HOXA9 tumor DNA as a biomarker for mortality in recurrent breast cancer.
Authors: Torben Hansen, Stine Bakkensen Bakkensen Bruun, Rikke Fredslund Andersen, Jonna Skov Madsen, Tomasz Piotr Tabor, Troels Bechmann, Ina Mathilde Kjær
Journal: Journal of Clinical Oncology (2023)

e13106 Background: The Homeobox A9 (HOXA9) gene may act as a tumor suppressor in carcinomas and induce breast cancer progression. The clinical potential of methylated HOXA9 (meth-HOXA9) as a biomarker is unclear. Therefore, this study aims to examine the association between meth-HOXA9 in tumor tissue, meth-HOXA9 in plasma, and mortality. Additionally, the study examines the association between meth-HOXA9 in metastatic tissue and plasma at the time of recurrence. Methods: The study enrolled 51 patients with recurrent breast cancer between 2011 and 2015 recruited at the Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark. Tissue samples were obtained from the primary tumor at the time of primary surgery between 1993 and 2013. Tissue samples from the metastases and plasma samples were obtained at the time of recurrence. The study follow-up period ran until death or January 2019. All samples were analyzed for meth-HOXA9 using droplet digital PCR. The optimal cut-off for meth-HOXA9 in tissue was established at ≥7.4% using tissue specimens from independent breast cancer patients and healthy controls. In plasma samples, the detection of ≥5 meth-HOXA9-containing droplets resulted in a positive test. Using Cox regression, we estimated crude and age-adjusted hazard ratios (HR) for mortality with 95% confidence intervals (CI) comparing patients with detectable and undetectable meth-HOXA9 in both tumor tissue and plasma. Fischer’s exact test was used to compare plasma and metastasis meth-HOXA9 status. Results: Among the 50 patients with data on tumor tissue meth-HOXA9, 80% had detectable meth-HOXA9 in the primary tumor, but there was no increased mortality when comparing patients with detectable and undetectable meth-HOXA9 (HR 1.09; CI 0.47-2.52). Only 34 patients had data on plasma meth-HOXA9 and 62% of these had detectable meth-HOXA9 at the time of recurrence. Patients with detectable meth-HOXA9 in plasma had higher mortality than those without (HR 3.95; CI 1.50-10.37). Among the 20 patients with data on plasma and metastatic tissue meth-HOXA9, there was no significant association between meth-HOXA9 in plasma and metastatic tissue (p = 1.00). Conclusions: These results indicate that detectable plasma meth-HOXA9 at the time of breast cancer recurrence is associated with increased mortality. However, there is no association between tumor tissue meth-HOXA9 and mortality. Metastatic tissue and plasma meth-HOXA9 are not associated. Our data support the potential relevance of plasma meth-HOXA9 as a biomarker for prognosis and mortality in recurrent breast cancer, which calls for further investigation.
The impact of the 4R Oncology model of team-based care delivery on timing and sequence of guideline recommended interdependent care in breast and lung cancers.
Authors: Raymond Liu, Julia R. Trosman, Elizabeth Shurell Linehan, Nancy P. Gordon, Marti Hennings, Henie James, Thea Abbe, Jed Abraham Katzel, Chun Fai Ng, Megumi Tomita, Jeffrey B. Velotta, Lori C. Sakoda, Kimberly Beringer, Arliene Ravelo, Zheng Zhu, Bruce Rapkin, Christine B. Weldon
Journal: Journal of Clinical Oncology (2023)

1523 Background: Team-based care improves quality, reduces fragmentation and lowers clinician burnout related to ad hoc care coordination. A key principle of teamwork is managing timing and sequence of interdependent care (Vogel JOP 2016). The 4R Oncology model featured by the NCI ASCO Teams project fosters effective teamwork by facilitating systematic timing / sequence of interdependent care (Trosman JOP 2016). 4R is Right Info / Care / Patient / Time. Using 4R, a large health system created a high-functioning care team and conducted optimizations of interdependent care in breast and lung cancers Oct 2020 - Dec 2021 (Liu JCOOP 2022). Optimizations focused on guideline-based care with suboptimal timing / sequencing in respective cancers. We present results of these optimizations. Methods: We compared data from electronic health record on timing and sequence of care between historical control cohorts of patients who received care pre-4R (breast n=270, lung n=173) to the post-optimization 4R cohorts (breast n=208, lung n=139). Patient and tumor characteristics between control and 4R cohorts in both breast and lung cancers were similar. Results: Timing and sequence of care for 5 of the 6 breast cancer metrics and all 6 lung cancer metrics was significantly improved between the control and 4R cohorts. Despite significant increase, the rate of timely care for some metrics remained low, such as referrals based on distress screening in breast cancer and palliative care in lung cancer. Conclusions: The 4R Oncology model is effective in applying teamwork principles and improving timing and sequence of guideline-based care. Opportunities for further improvement exist to expand the benefit of 4R to a higher number of patients. A learning system being established in our institution will inform iterative care optimizations.[Table: see text]
Impact of state policies on telehealth use among the privately insured with newly diagnosed cancer.
Authors: Ya-Chen Tina Shih, I-Wen Pan, Tina W.F. Yen
Journal: Journal of Clinical Oncology (2023)

1607 Background: The COVID-19 public health emergency (PHE), declared on January 31, 2020, relaxed many telemedicine restrictions. Yet there remains wide variation across states on the coverage and reimbursement of telemedicine services and rules to permit practicing across state lines. Research has shown expanded access to telemedicine is beneficial to cancer patients, making it important to understand the relationship between state policies and the use of telemedicine. Methods: We identified privately insured non-elderly patients newly diagnosed with any of five common cancers (female breast, prostate, lung, colorectal, and lymphoma) between March 2019 and March 2021 from Optum Clinformatics Data Mart. We characterized state telehealth policies by parity status (coverage &amp; payment parity, coverage parity only, and none) and rules for cross-state practice (allowed with vs. without limitations). We applied interrupted time series analysis to examine the trend of telemedicine use before and after the declaration of COVID-19 PHE and conducted multivariable logistic regression to examine the association between state policies and telemedicine use while controlling for other confounders. Results: Of the 10,813 privately insured non-elderly patients, the adjusted rate of telemedicine use was 23.6%. The average age was 53.2 (SD = 9.24). Race/ethnicity distribution was 71.20% non-Hispanic White, 10.07% non-Hispanic Black, 8.56% Hispanics, 3.77% Asians, and 6.39% others. Lymphoma, female breast, colorectal, lung, and prostate cancer accounted for 10.55%, 46.55%, 13.27%, 7.56%, and 22.07% of patients. A sharp increase was observed early on (from 32.4% in March 2020 to 42.5% in April 2020), followed by a steady decline, down to &lt; 15% by March 2021. Compared to patients residing in states with coverage and payment parity, those in states with only coverage parity and no parity were significantly less likely to use telemedicine (OR = 0.79, 95% CI: [0.71 – 0.88]; OR = 0.77, [0.68 – 0.87]). Patients residing in states with more restrictions/regulations on cross-state practice were significantly less likely to use telemedicine (OR = 0.84, [0.76 – 0.93]) than those in states that were less restrictive. Other factors predicting lower likelihood of telemedicine use included older age (OR = 0.69 [0.62-0.77] for age 50-64 vs. 20-49), non-Hispanic Black (OR = 0.84 [0.72 – 0.98] vs. non-Hispanic White), colorectal cancer (OR = 0.82 [0.70 – 0.96] vs. female breast), and more recent diagnosis. Conclusions: With the approaching end of COVID-19 PHE, states are deciding whether to permanently relax certain telemedicine policies or return to existing more restrictive policies. Our study suggests patients residing in states that move toward less generous parity and more restrictive cross-state practice rules may be less likely to benefit from telemedicine.
BMI and mortality in hormone-negative breast cancer: A PLCO trial subgroup analysis.
Authors: Reem Chamseddine, Stella Major, Arash Rafii, Hind Doha Elmalik
Journal: Journal of Clinical Oncology (2023)

e12544 Background: Body Mass Index (BMI) is a significant prognostic factor in the survival of patients with hormone receptor-positive breast cancer (BC).[1-2] However, the relationship between BMI and survival is not well-established in hormone receptor-negative (HR-) breast tumors. [3] Emerging data is mixed: some studies show that BMI does not impact outcomes in HR- tumors [4], while others reveal worse survival in patients with elevated BMI.[5] In this study, our objective was to corroborate recent evidence about the relationship between BMI and mortality in hormone-negative breast cancer. Methods: We used the PLCO cancer screening trial, a publicly available database containing information about 155,000 participants enrolled in the United States between 1993 and 2001. Data were collected on cancer mortality through 2018 (median follow-up of 19.2 years post enrollment). The methodology of the PLCO trial has been described previously.[6] All female patients with a diagnosis of HR- BC diagnoses were selected for data retrieval, including HR-/HER2+ and HR-/HER2- tumors. Patients with equivocal receptor status were excluded. We used multivariate Cox regression to analyze mortality by BMI category, after adjusting for all significant variables at the bivariate level ( p &lt;0.25). Results: 348 women with confirmed HR- BC at the time of study participation were included. Mean age was 69 years old, and 62 patients (17.8%) passed away due to breast cancer during study enrollment or follow-up. Patients who were of normal weight (BMI 25-&lt;30) at age of trial enrollment were not significantly more likely to survive compared to overweight or obese patients (Hazard Ratio 1.274, p= 0.623). Conclusions: Our results show no significant relationship between BMI and mortality in patients with HR- BC tumors. This finding adds to the growing literature about weight status in hormone receptor-negative tumors. Our data suggests that the mechanism of tumor progression in HR- breast tumors is unlikely to involve signaling mechanisms in adipocytes. Clinical trial information: NCT00002540 , NCT01696968 , NCT01696981 , NCT01696994 . [Table: see text]
Feasibility of treatment with another CDK4/6 inhibitor after severe ribociclib liver toxicity.
Authors: Jean-Philippe Zurcher, Morgan Goujon, Paul H. Cottu, Isabelle Desmoulins, Luis Teixeira, Laura Mansi, Guillaume Meynard, Erion Dobi, Elise Rowinski, Marion Stacoffe, Paule Augereau, Marie Robert, Yann Mottaz, Anaïs Gaiffe, Aurélie Grandvuillemin, Mapi Fleury, Ana Dolcan, Athina Stravodimou, Khalil Zaman, Elsa Curtit
Journal: Journal of Clinical Oncology (2023)

e13067 Background: Ribociclib is, for now, the only CDK4/6 inhibitor having demonstrated a statistically significant increase of overall survival in first-line in hormone receptor-positive, HER2-negative advanced breast cancer. One of the limiting toxicities of ribociclib is the occurrence of grade III/IV hepatobiliary toxicity in approximately 5% of patients. It contraindicates the reintroduction of the drug. Therapeutic options after this type of adverse event are challenging because there are very limited data regarding cross reactivity in risk for hepatic injury between ribociclib, palbociclib or abemaciclib. Methods: We describe a cohort of 28 patients who presented with grade III and/or IV ribociclib-induced hepatitis and who subsequently received another CDK4/6 inhibitor. Cases were collected from the French pharmacovigilance database and additional cases were obtained through institutional databases. Data were retrospectively obtained from patients’ reports. Results: Twenty-eight patients, from 11 centers, presented a grade III (71%, 20 patients) or a grade IV (29%, 8 patients) transaminase elevation with ribociclib. Median transaminase elevation was 12.3 x ULN (upper limit normal) for AST and 15.2 x ULN for ALT. This toxicity occurred within the first 6 months of treatment for all patients except one. Ribociclib was associated with letrozole in 21 patients, fulvestrant in 5 patients and anastrozole or exemestane in 2 patients. No acute liver failure occurred. All patients switched to another CDK4/6 inhibitor (23 patients - 82% - palbociclib and 5 - 18% - abemaciclib) without significant reoccurrence of liver toxicities. Four patients (14%) presented a transient grade 1 or 2 hepatic toxicity (all of them with palbociclib), 20 patients (71%) received the second CDK4/6 inhibitor at full dose. The median follow-up was 16 months. Conclusions: Treatment with palbociclib or abemaciclib after grade III or IV transaminase elevation due to ribociclib is feasible and none of the patients in this cohort exhibited reoccurrence of significant liver toxicity afterwards. Ribociclib liver toxicity occurs mainly during the first 6 months of treatment and takes several months to recover. [Table: see text]